N- sulfonyl aldimines

More recently, in a series of papers Weinreb and coworkers have found that N-sulfonyl aldimines can in fact be rapidly produced in situ from aliphatic aldehydes using N-sulfinyl sulfonamides and boron trifluoride etherate as catalyst at low temperature [11-15] [Eq. (6)]. Similarly, aliphatic aldehydes can be converted to the N-sulfonyl imines in the absence of a Lewis acid at room temperature or above, but more slowly. The former procedure also works well for aromatic aldehydes, whereas the reaction is too slow to be useful if a Lewis acid is not used. The N-sulfonyl imines generated in this manner can be utilized in a number of transformations (vide infra). However, except in rare cases [16], AT-sul-fonyl ketimines cannot be formed by this methodology. 

Shono and coworkers have examined the electrochemical oxidation of sulfonamides [25], presumably with the intent of generating a-alkoxy sulfonamides. However, anodic oxidation of short chain acyclic sulfonamides, like 12, in the presence of halide ion surprisingly afforded the a-sulfonamido acetals 13 (Scheme 6) [25a]. It is believed that oxidation of 12 occurs to initially produce a-methoxy sulfonamide 14. Under the reaction conditions, however, 14 eliminates methanol to produce N-sulfonyl aldimine 15, which can tautomerize to ene sulfonamide 16. Reaction of 16 with a positive halogen species, generated elec-trochemically, probably leads to 17, which can rearrange via an intermediate aziridine to the observed acetal product 13. 

The rhodium-catalyzed addition of aryl- and 1-alkenylboronic acids tooc, unsaiurated ketones, aldehydes, esters, and amides gave the conjugate 1,4-addition products in high yidds. The ifaodium(I) complexes also catalyzed the 1,2-addition of organoboronic acids to aldehydes or N-sulfonyl aldimines. The dficiency of protocol was demonstrated in the asymmetric addition reactions of organoboronic acids in the presoice of a rhodium(acacV BINAP complex. 

It was recently found that the arylation of N-sulfonyl aldimines with arylboronic acids or esters can be carr d out in the presence of [Rh(codXMeCN ]BF4 (Scheme 17) (20). Arylboronic acids fr hly crystallized... 

Scheme 6.37 The enantioselective copper(ll)-catalyzed addition of indoles to N-sulfonyl aldimines, as described by Zhou s group [50].

Miyaura also [50] reported rhodium-catalyzed additions of arylboronic acids to aldimines. Despite the potential production of water from boronic adds by cydic trimerization, no hydrolysis of N-sulfonyl aldimines was observed when boronic acids were used in the rhodium-catalyzed addition to aldimines in anhydrous diox-ane. The reactions proceeded well, regardless of the presence of both an electron-withdrawing and an electron-donating group on the aldehyde or the arylboronic add. For example, the reaction of N-sulfonyl aldimine 79a with boronic acid 2o catalyzed by cationic rhodium [Rh(cod) MeCN)2]BF4 gave 87% yield of the product 80ao, and... 

Scheme4.38 Rhodium-catalyzed addition of organoboronic acids to N-sulfonyl aldimines.

Asymmetric Friedel-Crafts additions of indole (19) to N-sulfonyl aldimines (31) are also possible. Bn-BOX (32)/Cu(OTf)2 provides chiral 3-indolylmethanamine derivatives (33) in moderate to good yields and excellent enantioselectivities (Scheme 17.6) [11]. 

Extension of this work to the diastereoselective synthesis of y-lactams from N-sulfonyl aldimines [93] and ketimines [94] was subsequently reported. Scheldt and coworkers disclosed an enantioselective version (up to 98% ee) from reactive hydrazones in the initial demonstration of cooperative NHC/Lewis acid catalysis using a bulky, chiral triazolium salt and catalytic Mg(OBu )2 [95]. Rovis and coworkers synthesized y-lactams 109 enantioselectively using a chiral N-C Fs triazolium salt (Scheme 18.19). A weak carboxylate base was sufficient to partially deprotonate the precatalyst 108 in situ, and the carboxylic acid formed could activate the N-Ar imine acceptor 107 via protonation [lib]. In all these cases, a fine balance must exist between sufficient electrophilicity vis-a-vis the competing enal and reversible addition of the carbene to the imine/hydrazone/iminium or to the Lewis acid. 

The stereochemical outcome in these additions can be understood by invoking Cram chelate [48] and Felkin-Anh-type [49] transition states for N-benzyl and N-sulfonyl aldimines, respectively (Figure 11.2 see also Chapter 2). The consequences of these results and their applications are noteworthy. Thus, selection of the appropriate N-protecting group can lead to preferential formation of either syn or anti 1,2-diamines at will [46]. 

Quinazolinones are an important class of fused heterocycles that have been reported with remarkable activities in biology and pharmacology such as anticancer, antiinflammatory, anticonvulsant, antibacterial, antidiabetic, hypolipidemic, and protein tyrosine kinase inhibitors. Alper and Zheng reported a palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides to produce quinazolin-4(3H)-ones in 2008. A wide variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields (Scheme 3.27a). The reaction is believed to proceed via in situ formation of an amidine, followed by oxidative addition, CO insertion, and intramolecular cyclization to give the substituted quinazolin-4(3H)-ones. Later on, a procedure was established based on generating the amidine in situ by a copper-catalyzed reaction of terminal allq nes, sulfonyl azide and o-iodo-anilines. The desired quinazolinones can be produced by carbonylation with Pd(OAc)2-DPPB-NEt3-THF as the reaction system. In the same year, Alper s group developed a procedure for 2,3-dihydro-4(lH)-quinazolinone preparation. The reaction started with the reaction of 2-iodoanilines and N-toluenesulfonyl aldimines followed by palladium-catalyzed intramolecular... 

Carretero and coworkers have successfully employed a copper(I)-Fesulphos complex as a Lewis acid for enantioselective Mannich-type reactions of N-sulfonyl imines [43]. A combination of [151 CuBr]2 and AgCl04 does efficiently catalyze the addition of silyl enol ethers of ketones, esters, and thioesters (150) to N-(2-thienyl)sulfonyl aldimines (Scheme 17.30). The corresponding P-amino carbonyl derivatives (152) were isolated in good yields with generally good enan-tioselectivity. 

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